Epstein Barr virus shedding in multiple sclerosis: similar frequencies of EBV in saliva across separate patient cohorts

Background: Epstein Barr Virus (EBV) infection is closely associated with multiple sclerosis (MS), but the relationship between viral load and disease activity is unclear. This study tested the observed levels of salivary EBV in MS, as a first step in investigating this relationship. Methods: Real-time quantitative PCR (qPCR) was used to measure EBV DNA levels in saliva samples from three separate Multiple Sclerosis (MS) patient cohorts. Results: The qPCR assay was used to delineate EBV shedding, defined here as a reliably detectable level of extracellular EBV DNA in saliva. Frequency of EBV shedding was found to be similar across the groups, with 20–25% of subjects releasing virus on any given sampling date. Diurnal variation in EBV count was tested in one of the cohorts, in which 26% of subjects showed more than a 10-fold difference between the highest and lowest EBV levels on a single day. In the same cohort, elevated viral levels at one time point did not predict elevated viral levels at a subsequent time point. Conclusions: These results indicate that EBV lytic activity in a subject cannot be inferred from a single measure of EBV in saliva. Also, subjects do not appear to be behave constantly as “EBV shedders” or “non-shedders”. The assay is useful in giving a clear indication of salivary gland EBV lytic activity across a patient cohort – for example, in testing anti-viral drugs in M

Particulate matter and risk of parkinson disease in a large prospective study of women

Background: Exposure to air pollution has been implicated in a number of adverse health outcomes and the effect of particulate matter (PM) on the brain is beginning to be recognized. Yet, no prospective study has examined the association between PM and risk of Parkinson Disease. Thus, our goal was assess if exposure to particulate matter air pollution is related to risk of Parkinson’s disease (PD) in the Nurses’ Health Study (NHS), a large prospective cohort of women. Methods: Cumulative average exposure to different size fractions of PM up to 2 years before the onset of PD, was estimated using a spatio-temporal model by linking each individual’s places of residence throughout the study with location-specific air pollution levels. We prospectively followed 115,767 women in the NHS, identified 508 incident PD cases and used multivariable Cox proportional hazards models to estimate the risk of PD associated with each size fraction of PM independently. Results: In models adjusted for age in months, smoking, region, population density, caffeine and ibuprofen intake, we observed no statistically significant associations between exposure to air pollution and PD risk. The relative risk (RR) comparing the top quartile to the bottom quartile of PM exposure was 0.99 (95% Confidence Intervals (CI): 0.84,1.16) for PM10 (≤10 microns in diameter), 1.08 (95% CI: 0.81, 1.45) for PM2.5 (≤2.5 microns in diameter), and 0.92 (95% CI: 0.71, 1.19) for PM10–2.5 (2.5 to 10 microns in diameter). Conclusions: In this study, we found no evidence that exposure to air pollution is a risk factor for PD

A Prospective Analysis of Airborne Metal Exposures and Risk of Parkinson Disease in the Nurses’ Health Study Cohort

Background: Exposure to metals has been implicated in the pathogenesis of Parkinson disease (PD). Objectives: We sought to examine in a large prospective study of female nurses whether exposure to airborne metals was associated with risk of PD. Methods: We linked the U.S. Environmental Protection Agency (EPA)’s Air Toxics tract-level data with the Nurses’ Health Study, a prospective cohort of female nurses. Over the course of 18 years of follow-up from 1990 through 2008, we identified 425 incident cases of PD. We examined the association of risk of PD with the following metals that were part of the first U.S. EPA collections in 1990, 1996, and 1999: arsenic, antimony, cadmium, chromium, lead, manganese, mercury, and nickel. To estimate hazard ratios (HRs) and 95% CIs, we used the Cox proportional hazards model, adjusting for age, smoking, and population density. Results: In adjusted models, the HR for the highest compared with the lowest quartile of each metal ranged from 0.78 (95% CI: 0.59, 1.04) for chromium to 1.33 (95% CI: 0.98, 1.79) for mercury. Conclusions: Overall, we found limited evidence for the association between adulthood ambient exposure to metals and risk of PD. The results for mercury need to be confirmed in future studies. Citation: Palacios N, Fitzgerald K, Roberts AL, Hart JE, Weisskopf MG, Schwarzschild MA, Ascherio A, Laden F. 2014. A prospective analysis of airborne metal exposures and risk of Parkinson disease in the Nurses’ Health Study Cohort. Environ Health Perspect 122:933–938; http://dx.doi.org/10.1289/ehp.130721

Perinatal Air Pollutant Exposures and Autism Spectrum Disorder in the Children of Nurses’ Health Study II Participants

Objective: Air pollution contains many toxicants known to affect neurological function and to have effects on the fetus in utero. Recent studies have reported associations between perinatal exposure to air pollutants and autism spectrum disorder (ASD) in children. We tested the hypothesis that perinatal exposure to air pollutants is associated with ASD, focusing on pollutants associated with ASD in prior studies. Methods: We estimated associations between U.S. Environmental Protection Agency–modeled levels of hazardous air pollutants at the time and place of birth and ASD in the children of participants in the Nurses’ Health Study II (325 cases, 22,101 controls). Our analyses focused on pollutants associated with ASD in prior research. We accounted for possible confounding and ascertainment bias by adjusting for family-level socioeconomic status (maternal grandparents’ education) and census tract–level socioeconomic measures (e.g., tract median income and percent college educated), as well as maternal age at birth and year of birth. We also examined possible differences in the relationship between ASD and pollutant exposures by child’s sex. Results: Perinatal exposures to the highest versus lowest quintile of diesel, lead, manganese, mercury, methylene chloride, and an overall measure of metals were significantly associated with ASD, with odds ratios ranging from 1.5 (for overall metals measure) to 2.0 (for diesel and mercury). In addition, linear trends were positive and statistically significant for these exposures (p < .05 for each). For most pollutants, associations were stronger for boys (279 cases) than for girls (46 cases) and significantly different according to sex. Conclusions: Perinatal exposure to air pollutants may increase risk for ASD. Additionally, future studies should consider sex-specific biological pathways connecting perinatal exposure to pollutants with ASD

Influence of partial replacement of olive oil on frying performance of palm olein

The influence of partial replacement of palm olein (POo) with olive oil (Oo), (25 and 50%, w/w) was investigated during five consecutive days of frying. The results indicated that frying performance of POo was significantly (P < 0.05) influenced by partial replacement with olive oil. The highest change in peroxide value (PV), anisidine value (AV), totox value (TV), total polar compound (TPC), viscosity and melting point was shown by the control sample; whereas the replacement of 50% (w/w) palm olein with 50% (w/w) olive oil exhibited the least changes in PV, AV, TV, TPC, viscosity and melting point during the frying process. This study suggests that the partial replacement of palm olein containing a high proportion of saturated fatty acids (i.e., palmitic acid) with olive oil containing a high content of monounsaturated fatty acid (i.e., oleic acid) can provide oil blends with higher chemical stability against oxidation. On the other hand, the prepared oil blend remained liquid at ambient temperature, thereby enhancing the physical stability induced by partial replacement with olive oil

Neonatal vitamin D status is not associated with later risk of type 1 diabetes:results from two large Danish population-based studies

Aims/hypothesis: The aim of this work was to assess whether neonatal levels of 25-hydroxyvitamin D (25(OH)D) are associated with risk of developing type 1 diabetes before the age of 18 years. Methods: Two large-scale studies with different designs—a case-cohort and a case–control—were conducted using Danish national register data and biobank material. Weighted Cox regression and conditional logistic regression were used to calculate HRs and ORs, respectively. The concentration of 25(OH)D was assessed from neonatal dried blood spots using highly sensitive liquid chromatography–tandem mass spectrometry. Quintiles of 25(OH)D3were used in the main analyses. Results: The case-cohort study included 912 type 1 diabetes cases and 2866 individuals without type 1 diabetes born in Denmark between 1981 and 2002 and followed up until the end of 2012. The case–control study included 527 matched case–control pairs born between 1981 and 1999 and followed up until May 2004. Both studies found no association between 25(OH)D3levels and later risk of developing type 1 diabetes. The neonatal total 25(OH)D levels in the studies were low: 46% (case-cohort study) and 51% (case–control study) of individuals had 25(OH)D levels &lt;25 nmol/l. Conclusions/interpretation: Our two large-scale national studies showed that 25(OH)D3levels around the time of birth were not associated with later type 1 diabetes risk. Whether higher levels of 25(OH)D3during pregnancy, acquired by higher doses of supplementation than are recommended today in most countries, could protect the offspring against type 1 diabetes cannot be ruled out by the present studies. © 2016, Springer-Verlag Berlin Heidelberg

Peripheral blood biomarkers in multiple sclerosis.

Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. The heteroge-neity of pathophysiological processes in MS contributes to the highly variable course of the disease and unpre-dictable response to therapies. The major focus of the research on MS is the identification of biomarkers inbiologicalfluids, such as cerebrospinalfluid or blood, to guide patient management reliably. Because of the diffi-culties in obtaining spinalfluid samples and the necessity for lumbar puncture to make a diagnosis has reduced,the research of blood-based biomarkers may provide increasingly important tools for clinical practice. However,currently there are no clearly established MS blood-based biomarkers. The availability of reliable biomarkerscould radically alter the management of MS at critical phases of the disease spectrum, allowing for interventionstrategies that may prevent evolution to long-term neurological disability. This article provides an overview ofthis researchfield and focuses on recent advances in blood-based biomarker researc

Molecular mechanism underlying the impact of vitamin D on disease activity of MS

Objective: Some previous studies suggest modest to strong effects of 25-hydroxyvitamin D (25(OH)D) on multiple sclerosis (MS) activity. The objective of this study was to explore the mechanistic rationale that may explain potential clinical effects of 25(OH)D. Methods: This study measured serum 25(OH)D levels and global gene expression profiles over a course of up to 2 years in patients starting treatment with interferon beta-1b (IFNB-1b) after a clinically isolated syndrome. MS disease activity was assessed by the number of gadolinium-enhancing lesions present on repeated magnetic resonance imaging (MRIs). Results: The number of gadolinium-enhancing lesions was highly significantly associated with 25(OH)D levels. Conducting various systems-level analyses on the molecular level, multiple lines of evidence indicated that 25(OH)D regulates expression dynamics of a large gene–gene interaction system which primarily regulates immune modulatory processes modulating MS activity. The vitamin D response element was significantly enriched in this system, indicating a direct regulation of this gene interaction network through the vitamin D receptor. With increasing 25(OH)D levels, resulting regulation of this system was associated with a decrease in MS activity. Within the complex network of genes that are regulated by 25(OH)D, well-described targets of IFNB-1b and a regulator of sphingosine-1-phosphate bioavailability were found. The 25(OH)D effects on MS activity were additively enhanced by IFNB-1b. Interpretation Here, we provide mechanistic evidence that an unbalanced 25(OH)D gene expression system may affect MS activity. Our findings support a potential benefit of monitoring and managing vitamin D levels (e.g., through supplementation) in early MS patients treated with IFN-beta-1b